In this project we are coupling genetic and environmental studies in selected families, twin pairs and populations with disorders such as multiple sclerosis, Parkinson's disease, and Alzheimer's disease, in an effort to distinguish specific contributing factors. Multi-disciplinary twin studies of Parkinson's disease, multiple sclerosis and Alzheimer's disease indicate each is complex and involves an interaction of environmental and genetic factors. A study similar in design involving twins with documented polio over 30 years ago is designed to look at factors contributing to 'post polio' syndrome. An autosomal dominant, hereditary leukoencephalopathy simulating MS with onset at about age 35 is under study in a kindred with over 20 affected. Derangement of the autonomic nervous system is often seen early in the course and when recognized clinically, serves to distinguish this single gene disorder from multiple sclerosis. In Saudi Arabia a multidisciplinary study of an extended kindred with an autosomal recession form of muscular dystrophy is planned. Epidemiologists and geneticists working together will assess the relative burden of environmental and genetic factors in this highly inbred population from the Western part of the Kingdom.